Sevoflurane (fluoromethyl-1,1,1,3,3,3-hexafluoroisopropyl ether) is an inhalation anesthetic and is described in U.S. Pat. No. 3,689,571 which is incorporated herein by reference. U.S. Pat. Nos. 4,250,334 and 4,469,898 describe techniques for producing sevoflurane. The '334 and '898 patents also are incorporated herein by reference. The techniques described in these patents utilize hexafluoroisopropyl alcohol (HFIP) as a starting material. The '898 patent describes a technique in which HFIP is combined with formaldehyde, hydrogen fluoride, and a protonating, dehydrating and fluoride ion-generating agent. The '334 patent describes a technique in which HFIP is added to a mixture of a stoichiometric excess of paraformaldehyde and hydrogen fluoride, plus sufficient sulfuric acid to sequester most of the water produced by the reaction.
Sevoflurane produced in accordance with the techniques described in the '334 and '898 patents must undergo additional purification steps due to the fact that the polyacetal formed in the first step of the described techniques is cleaved into numerous by-products, primarily fluorinated bis-ethers. Such by-products can be difficult to remove from the reaction solution. Further, the use of corrosive materials such as hydrogen fluoride and sulfuric acid requires that specialized equipment and special handling precautions be employed during the described processes, thereby increasing the cost of sevoflurane production.
It is desirable to provide a process that produces sevoflurane in relatively high yields, i.e., at least about 80% yields. It also is desirable to provide a process that is relatively simple, i.e., a process that requires a minimum number of steps and a minimum number of reaction vessels. Finally, it is desirable to provide a process for producing sevoflurane that utilizes commercially available, non-corrosive, and relatively inexpensive materials.